Baculovirus Displaying Hemagglutinin Elicits Broad Cross-Protection against Influenza in Mice

PLoS One. 2016 Mar 29;11(3):e0152485. doi: 10.1371/journal.pone.0152485. eCollection 2016.

Abstract

The widespread influenza virus infection further emphasizes the need for novel vaccine strategies that effectively reduce the impact of epidemic as well as pandemic influenza. Conventional influenza vaccines generally induce virus neutralizing antibody responses which are specific for a few antigenically related strains within the same subtype. However, antibodies directed against the conserved stalk domain of HA could neutralize multiple subtypes of influenza virus and thus provide broad-spectrum protection. In this study, we designed and constructed a recombinant baculovirus-based vaccine, rBac-HA virus, that expresses full-length HA of pandemic H1N1 influenza virus (A/California/04/09) on the viral envelope. We demonstrated that repeated intranasal immunizations with rBac-HA virus induced HA stalk-specific antibody responses and protective immunity against homologous as well as heterosubtypic virus challenge. The adoptive transfer experiment shows that the cross-protection is conferred by the immune sera which contain HA stalk-specific antibodies. These results warrant further development of rBac-HA virus as a broad-protective vaccine against influenza. The vaccine induced protection against infection with the same subtype as well as different subtype, promising a potential universal vaccine for broad protection against different subtypes to control influenza outbreaks including pandemic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Adoptive Transfer
  • Animals
  • Antibody Specificity / immunology
  • Baculoviridae / metabolism*
  • Bronchoalveolar Lavage Fluid
  • Cross Protection / immunology*
  • Female
  • HEK293 Cells
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Humans
  • Immune Sera / immunology
  • Immunity, Humoral
  • Immunization
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H5N1 Subtype / immunology
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / virology*
  • Recombination, Genetic / genetics
  • Spleen / pathology

Substances

  • Hemagglutinin Glycoproteins, Influenza Virus
  • Immune Sera

Grants and funding

JC received funding for this work from the Transgovernmental Enterprise for Pandemic Influenza in Korea which part of Korea Healthcare technology R&D Project by Ministry of Health & Welfare‚ Republic of Korea (Grant number: A103001) and the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (Grant number: HI13C0826). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.